Posted: Friday, April 15, 2022
According to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 4195/3), patients with multiple myeloma may benefit from a combination treatment of the SINE inhibitor selinexor plus the PI3K inhibitor duvelisib. Haiming Chen, MD, PhD, of the Institute for Myeloma & Bone Cancer Research in Los Angeles, and colleagues sought to determine the effectiveness of metronomic selinexor with or without duvelisib.
“This study illustrates that the combination of selinexor and duvelisib showed enhanced cytotoxic effects in vitro compared with single-agent treatment, and we will further evaluate the anti-[multiple myeloma] effects of selinexor in combination with duvelisib in vivo using our human [multiple myeloma] xenograft models,” concluded the authors.
The in vitro portion of the study isolated primary tumor cells from the bone marrow aspirates of patients with multiple myeloma and sourced the human multiple myeloma cell line U266 from the American Type Culture Collection. MTS assays used to determine cell viability indicated that concentration-dependent inhibition of cell proliferation in the cell line MM1s was induced by selinexor treatment at 0.1, 0.4, and 1.6 μM. At 0.2 μM, selinexor monotherapy was shown to reduce tumor cell proliferation in mononuclear cells obtained from a patient with progressive disease. A combination treatment that included a fixed amount of selinexor plus increasing quantities of duvelisib over a 48-hour period appeared to result in enhanced cytotoxic effects dependent on concentration.
Selinexor plus dexamethasone therapy was evaluated in vivo among SCID mice into which the human myeloma xenograft LAGκ-2 had been implanted. Tumor growth was more effectively hindered when the combination treatment was administered more frequently in lower doses than less frequently in mid-range or higher doses.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.